AJP - Regulatory, Integrative and Comparative Physiology, Vol 270, Issue 2 443-R449, Copyright © 1996 by American Physiological Society

ARTICLES

Lateral hypothalamic NMDA receptors and glutamate as physiological mediators of eating and weight control

B. G. Stanley, V. L. Willett 3rd, H. W. Donias, M. G. Dee 2nd and M. A. Duva
Department of Neuroscience, University of California, Riverside 92521, USA.

To determine whether endogenous lateral hypothalamic (LH) glutamate and its N-methyl-D-aspartate (NMDA) receptors might participate in the stimulation of natural eating, LH injection of the NMDA antagonist D-(-)-2-amino-5-phosphonopentanoic acid (D-AP5) was tested in adult male rats for suppressive actions on feeding elicited by 1) NMDA, kainic acid or D, L-alpha-amino-3-hydroxy-5-methylisoxazole (AMPA) injected into the LH; 2) food deprivation; and 3) the onset of the nocturnal period. D-AP5 (10-100 nmol) reduced by 72-90% the approximately 10-g eating response elicited by NMDA (10 nmol) without affecting the quantitatively similar eating responses elicited by kainic acid (1.0 nmol) or AMPA (1.0 nmol). This treatment also suppressed deprivation-induced eating by as much as 61% and nocturnal eating by as much as 40%. To determine its long-term effects, D-AP5 (50 nmol) was injected bilaterally into the LH twice a day for 8 consecutive days. This treatment caused up to 65% reductions in daily food intake and body weight loss of up to 13 g/day. These findings, showing behaviorally selective suppressions of eating and body weight by D-AP5, argue that endogenous LH glutamate acts to regulate natural eating and body weight and that NMDA receptors participate in these functions.

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